According to the National Center for Health Statistics, cardiovascular disease is the leading cause of death in the U.S. Over 70% of these deaths are related to atherosclerosis, and atherosclerotic cerebrovascular disease is a leading cause of death and major disability among adults. Thrombolic events originating in the bifurcation region of the carotid artery are a major cause of stroke. Currently some 140,000 carotid endarterectomy (CEA) surgeries are performed annually in the U.S. to prevent these events. A non-invasive, lower-cost alternative will be developed at University of Washington's Vascular Imaging Lab (VIL). The purpose of our research is to develop such a non-invasive imaging tool that can identify and characterize the features of carotid atherosclerotic plaque that signal imminent rapid lesion progression and ischemic complications. The specific aims are to: 1. Optimize MRI techniques for probing the luminal surface conditions and tissue composition of atherosclerotic carotid arteries on 3T. 2. Develop an MRI- based carotid artery scoring (CAS) system based on luminal and juxtaluminal surface conditions. 3. Optimize the weightings applied to various juxtaluminal characteristics in the CAS system. 4. Test the CAS for predicting progression or ischemic events within enrolled atherosclerotic patients in a prospective study. We will test the hypothesis that juxtaluminal characteristics are the primary determinants of carotid plaque progression and vulnerability to rupture. MRI imaging in combination with non-invasive in vivo histology will provide accurate information on plaque morphology and tissue composition, especially at the boundaries of the vessel wall and lumen. Improved methods of identifying high-risk plaques will result in: 1) better selection of patients for intervention; 2) development of an accurate, reproducible, and quantitative technique for directly assessing the status and progression of atherosclerotic lesions, significantly reducing the cost of clinical trials; 3) a unique opportunity to examine the processes involved in the progression from a stable lesion to vulnerable plaque. [unreadable] [unreadable] [unreadable]